Tepmetko (tepotinib) / EMD Serono - LARVOL DELTA

Real-world clinical, molecular, treatment patterns and outcomes of rare mutations in lung cancer from community oncology centres in Western India (ELCC 2026) - "Among mutated cases receiving targeted therapy, MET alterations (n=12) were treated with crizotinib, capmatinib & tepotinib (each n=4); KRAS co-mutations (n=13) mainly received bevacizumab-based regimens (n=6), followed by trametinib (n=2) & Nintedanib (n=1); BRAF-altered tumors (n=7) were mainly treated with chemotherapy & few were targeted with dabrafenib + trametinib (n=3); RET mutations (n=8) received cabozantinib & selpercatinib (each n=3); HER2 alterations (n=21) were mainly managed with trastuzumab -based regimens (n=13). With a median follow-up of 16.3 months, median overall survival (mOS)for the cohort was 13.9 mo(95% CI 10.6–17.1; mOS for single mutation was 15.9 mo vs 12.3 mo for co-mutations (p=0.637).mOS by mutation subtype was 14.3 mo (95% CI 0.0–68.6) for MET, 35.0 mo (95% CI NA–NA) for RET, 13.7 mo (95% CI 8.7–18.7) for BRAF, 10.3 mo (95% CI 2.4–18.2) for HER2, while KRAS/TP53 mutations had mOS of 13.1mo (95% CI 9.4–16.8).Conclusions This..."

Clinical • IO biomarker • Real-world • Real-world evidence • Lung Cancer • Oncology • Solid Tumor • ALK • BRAF • EGFR • HER-2 • KRAS • MET • PD-L1 • RET • ROS1 • TP53

Real-world outcomes (RWO) of oral MET-inhibition in EGFR MET-amplified (MET-amp) NSCLC (ELCC 2026) - "Treatment regimens included tepotinib (tepo) with osimertinib (Osi) (n=14), capmatinib (Cap) with nazartinib (n=3), savolitinib with Osi (n=1), vebreltinib with Osi (n=1), Cap with Erlotinib/Gefitinib (n=3). MET-treated patients with MET:CEP7 ratio ≥2 (n=10) had similar responses to those with ratio <2 (n=5) (mOS 45.4 vs 49.8m, mPFS on MET-i 8.2 v 6.8m, DOR 8.9 v 6.2m).Conclusions Combination EGFR and MET inhibition benefited both denovo Met-amp and post TKI MET resistant EGFR patients. Oral combinations remain an important option for patients."

Clinical • Real-world • Real-world evidence • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • EGFR

Tepotinib in patients (pts) with METexon 14 (METex14) skipping non-small cell lung cancer (NSCLC) from the VISION study: ≥3-year follow-up outcomes (ELCC 2025) - P2 | "In VISION pts with ≥3-years follow-up, tepotinib continued to demonstrate robust and durable activity across treatment lines. Importantly, outcomes in pts with METex14 skipping were consistent with previous results, reinforcing tepotinib as a meaningful treatment option in this setting."

Clinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

Real-World Evidence for 10 Oncology Drugs Approved in the last 5 years: A Comprehensive Narrative Synthesis. (PubMed, Crit Rev Oncol Hematol) - "RWE confirms the effectiveness and safety of multiple recently approved oncology drugs reinforcing the external validity of RCTs."

HEOR • Journal • Real-world evidence • Review • Breast Cancer • Endometrial Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Microsatellite Instability • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Urothelial Cancer • ER • HER-2 • MSI

Regulatory divergence in EMA approvals for targeted therapies in oncogene addicted NSCLC (ESMO-TAT 2026) - "Investigation of the factors behind divergent regulatory outcomes could help clarify the regulatory pathway for future drugs targeting molecularly-defined subsets of NSCLC. Comparative review of CHMP/EC documents and EPARs for crizotinib (Xalkori®), entrectinib (Rozlytrek®), repotrectinib (Augtyro®), sotorasib (Lumykras®), adagrasib (Krazati®), selpercatinib (Retsevmo®), pralsetinib (Gavreto®), trastuzumab deruxtecan (Enhertu®), tepotinib (Teptmeko®) and capmatinib (Tabrecta®). EMA approvals for oncogene-addicted NSCLC show inconsistency across biomarkers. A clear and consistent application of a framework for small-population settings is essential to (1) define when ORR/DoR benchmarks from robust single-arm studies justify line-agnostic approval; (2) align post-authorisation obligations to residual uncertainty; and (3) enable a similar developmental approach to first- and later line targeted therapies that address unmet..."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HER-2 • KRAS • MET • ROS1

EGFR and MET mRNA overexpression in non-small cell lung cancer: Prevalence and sensitivity to targeted therapies (ESMO-TAT 2026) - "MET-overexpressing models were highly sensitive to MET inhibition by tepotinib and capmatinib, with approximately 70% reduction in viability at <0.1 μM concentration, and one model showed sensitivity to the telisotuzumab vedotin, a MET ADC. The EGFR-overexpressing model exhibited strong sensitivity to afatinib and zipalertinib, whereas the anti-EGFR antibody cetuximab induced limited growth inhibition. mRNA overexpression of MET and EGFR identifies a small subset of NSCLC patients which may represent potential candidates for targeted treatment. mRNA overexpression of MET and EGFR identifies a small subset of NSCLC patients which may represent potential candidates for targeted treatment. Patient-derived 3D cultures confirmed that MET-overexpressing models are sensitive to MET inhibitors and to telisotuzumab-vedotin, while EGFR-overexpressing models show sensitivity to EGFR TKIs and limited response to the anti-EGFR antibody cetuximab. These findings support the..."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

MET-Driven Resistance to Sotorasib in KRAS G12C-Mutant NSCLC and Response to Combined KRAS and MET Inhibition. (PubMed, JTO Clin Res Rep) - "Notably, one patient with acquired MET amplification achieved a renewed partial response to the combination of sotorasib and tepotinib after progression on sotorasib monotherapy. Our findings support rebiopsy at progression on sotorasib. Further prospective trials are warranted to validate MET amplification as a resistance mechanism and to define optimal therapeutic thresholds for combined KRAS and MET inhibition."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

Tepotinib Phase II in NSCLC Harboring MET Alterations (VISION) (clinicaltrials.gov) - P2 | N=337 | Active, not recruiting | Sponsor: EMD Serono Research & Development Institute, Inc. | Trial completion date: Feb 2025 ➔ Oct 2025

Trial completion date • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

Tepotinib Phase II in NSCLC Harboring MET Alterations (VISION) (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: EMD Serono Research & Development Institute, Inc. | N=60 ➔ 120 | Trial primary completion date: Mar 2018 ➔ Dec 2018

Enrollment change • Trial primary completion date • Lung Adenocarcinoma • Non Small Cell Lung Cancer • MET

Tepotinib Phase II in NSCLC Harboring MET Alterations (VISION) (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: EMD Serono Research & Development Institute, Inc. | Trial primary completion date: Dec 2018 ➔ Jun 2019

Trial primary completion date • Lung Adenocarcinoma • Non Small Cell Lung Cancer • MET

Tepotinib Phase II in NSCLC Harboring MET Alterations (VISION) (clinicaltrials.gov) - P2 | N=337 | Active, not recruiting | Sponsor: EMD Serono Research & Development Institute, Inc. | Trial completion date: Feb 2023 ➔ Feb 2025

Trial completion date • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

Tepotinib Phase II in NSCLC Harboring MET Alterations (VISION) (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: EMD Serono Research & Development Institute, Inc. | N=60 ➔ 120

Enrollment change • Lung Adenocarcinoma • Non Small Cell Lung Cancer • MET

Tepotinib Phase II in NSCLC Harboring MET Alterations (VISION) (clinicaltrials.gov) - P2 | N=280 | Recruiting | Sponsor: EMD Serono Research & Development Institute, Inc. | N=120 ➔ 280 | Trial completion date: Dec 2019 ➔ Feb 2023 | Trial primary completion date: Jun 2019 ➔ Dec 2021

Enrollment change • Trial completion date • Trial primary completion date • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer • MET

Tepotinib Phase II in NSCLC Harboring MET Alterations (VISION) (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: EMD Serono Research & Development Institute, Inc. | N=120 ➔ 60

Enrollment change • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

Tepotinib Phase II in NSCLC Harboring MET Alterations (VISION) (clinicaltrials.gov) - P2 | N=337 | Active, not recruiting | Sponsor: EMD Serono Research & Development Institute, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

Tepotinib Phase II in NSCLC Harboring MET Alterations (VISION) (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: EMD Serono Research & Development Institute, Inc.

New P2 trial • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

Efficacy and safety of tepotinib in MET‑altered non‑small cell lung cancer: a meta-analysis. (PubMed, Sci Rep) - No abstract available

Journal • Retrospective data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Successful treatment with tepotinib followed by pembrolizumab in pulmonary pleomorphic carcinoma harbouring a MET exon 14 skipping mutation: A case report. (PubMed, Oncol Lett) - "Although the tumour relapsed 4 months postoperatively, treatment with tepotinib resulted in a favourable response and subsequent pembrolizumab therapy achieved a durable response. This case suggests that patients with sarcomatoid carcinoma, which is generally associated with a poor prognosis, may experience improved outcomes with the use of molecular targeted therapies and immune checkpoint inhibitors."

IO biomarker • Journal • Lung Cancer • Oncology • Sarcoma • Solid Tumor • MET

Lazertinib & Tepotinib for EGFR Mutant NSCLC in MET Overexpressed or Amplified Who Progressed After Lazertinib Treatment (clinicaltrials.gov) - P2 | N=47 | Recruiting | Sponsor: Samsung Medical Center | Not yet recruiting ➔ Recruiting

Enrollment open • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BRAF • EGFR • MET

Tepotinib Therapy for Advanced MET Exon 14 Skipping NSCLC With Non-Dialysis End-Stage Renal Disease: A Case Report. (PubMed, Respirol Case Rep) - "Tepotinib was resumed at a reduced dose without further renal deterioration, resulting in a partial tumour response. This case highlights the feasibility of tepotinib therapy in carefully selected patients with ESRD and underscores the clinical utility of incorporating complementary renal biomarkers, cystatin C, for guiding treatment decisions and avoiding unnecessary treatment discontinuation."

Journal • Acute Kidney Injury • Chronic Kidney Disease • Lung Cancer • Nephrology • Non Small Cell Lung Cancer • Oncology • Renal Disease • Solid Tumor • CST3 • MET

Phase II study of cabozantinib in patients with MET-altered lung cancers (ESMO 2023) - P2 | "Most pts (84%, 20/24) received a prior MET TKI (crizotinib, n=15; capmatinib, n=4; tepotinib, n=1); 16 pts (67%) and 13 pts (54%) received one or more prior lines of chemotherapy and immunotherapy, respectively...Due to its alternative type II binding mode, cabozantinib can be useful in the treatment of type I TKI resistance. As proof of concept, 3 of 4 responses were observed in patients with type I MET TKI progression."

Clinical • IO biomarker • P2 data • Lung Cancer • Oncology • Solid Tumor • MET

Targeting driver mutations in lung cancer with interstitial pneumonia: A nationwide study in Japan. (PubMed, Eur J Cancer) - "Multigene testing is underutilized in this population. While many targeted therapies carry a high risk of pneumonitis, sotorasib appeared relatively safe. Despite the risks, identifying and treating actionable oncogenic drivers may improve survival."

Journal • Fibrosis • Infectious Disease • Interstitial Lung Disease • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pneumonia • Respiratory Diseases • Solid Tumor • BRAF • EGFR • KRAS • MET

Tepotinib + osimertinib for EGFR mutant (EGFRm) NSCLC with MET amplification (METamp) after first-line (1L) osimertinib. (ASCO 2023) - P2 | "In this interim analysis of INSIGHT 2, tepotinib + osimertinib was highly active with durable responses, and was well tolerated in pts with EGFRm NSCLC with METamp after progression on 1L osimertinib. Tepotinib + osimertinib provides a potential chemotherapy-sparing oral targeted therapy option in this population with a high unmet need. Clinical trial information: NCT03940703."

Clinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • MET

Tepotinib + Osimertinib in EGFR-mutant NSCLC with MET Amplification Following 1L Osimertinib: INSIGHT 2 Primary Analysis (IASLC-WCLC 2023) - P2 | "Tepotinib + osimertinib demonstrated durable responses and a manageable safety profile in patients with EGFRm METamp NSCLC following 1L osimertinib, especially in Asian patients. Tepotinib + osimertinib provides a potential chemotherapy-sparing oral targeted therapy option in this population with a high unmet need."

Inflammation • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pneumonia • Solid Tumor • EGFR • MET

Tepotinib plus osimertinib in patients with EGFR-mutated non-small-cell lung cancer with MET amplification following progression on first-line osimertinib (INSIGHT 2): a multicentre, open-label, phase 2 trial. (PubMed, Lancet Oncol) - P2 | "Tepotinib plus osimertinib showed promising activity and acceptable safety in patients with EGFR-mutated NSCLC and MET amplification as a mechanism of resistance to first-line osimertinib, suggesting a potential chemotherapy-sparing oral targeted therapy option that should be further investigated."

Journal • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pneumonia • Pulmonary Disease • Respiratory Diseases • Solid Tumor • EGFR • MET